人类跨代效应研究的观察方法。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI:10.1080/15592294.2024.2366065
Rebecca Richards-Steed, Neng Wan, Amanda Bakian, Richard M Medina, Simon C Brewer, Ken R Smith, James A VanDerslice
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引用次数: 0

摘要

研究环境条件导致的人类跨代表观遗传结果面临巨大挑战。这项任务需要专门的方法和工具,这些方法和工具需要结合以下方面的具体知识:受试者及其祖先的多代关系组合、个体的表型数据、祖先及其后代的环境信息(可跨越历史到现在的数据集),以及在时间和空间上与祖先和后代一致的翔实环境数据。因此,对人类潜在的跨代影响的流行病学研究很少,从而限制了对祖先环境条件的了解,也限制了我们对现代人类健康结果所面临的潜在影响的了解。为了克服人类跨代效应研究中的一些挑战,我们提出了两种跨代研究设计:跨代时空聚类检测和跨代病例对照研究设计。与其他流行病学方法一样,这些方法可以确定受试者的表型结果(如不良健康结果)与其祖先面临的共同环境和环境因素之间是否存在统计学关联。当祖先是父系祖父母时,统计意义上的显著关联提供了一些证据,表明可能涉及跨代遗传因素。这种结果可能会产生有用的假设,可以利用表观基因组数据进行探讨,以确定跨代遗传效应的确凿证据。这两种方法都是以原发病例为中心的:它们都是围绕原发病例一代中感兴趣的表型设计的,用于病例选择和家系创建。在提供的例子中,我们在两种方法中都纳入了至少三代父系血统,以观察潜在的跨代效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Observational methods for human studies of transgenerational effects.

There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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